As end products of indole alkaloid biosynthesis in Vinca rosea the antineoplastic drugs vinblastine (1), vincristine (2) and related monomeric indole alkaloids will be examined for feedback inhibition both in intact tissue culture cells and subsequently on appropriate enzymes in this pathway. Initial in vivo tracer studies in the presence of exogenous alkaloid pools will be implemented to determine effects on various stages of the pathway. Information culled in this manner will be used to select enzymes with regulatory potential. Thus depending upon the stage of indole alkaloid biosynthesis found to be inhibited, enzymes occurring at bifurcation in the pathway, e.g. HMGCoA reductase, chorismate mutase, geraniol hydroxylase, loganic acid methyl transferase and secologanic acid reductase will be examined using kinetic analyses as well as other criteria for feedback control. Subsequently the manner of alkaloid binding to proteins will be investigated. Such a study may serve as a "model" system affording insight into the protein alkaloid interactions which occur in tumor cells.